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Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.
Facciotti, F; Larghi, P; Bosotti, R; Vasco, C; Gagliani, N; Cordiglieri, C; Mazzara, S; Ranzani, V; Rottoli, E; Curti, S; Penatti, A; Karnani, B; Kobayashi, Y; Crosti, M; Bombaci, M; van Hamburg, J P; Rossetti, G; Gualtierotti, R; Gerosa, M; Gatti, S; Torretta, S; Pignataro, L; Tas, S W; Abrignani, S; Pagani, M; Grassi, F; Meroni, P L; Flavell, R A; Geginat, J.
Afiliação
  • Facciotti F; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Larghi P; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Bosotti R; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Vasco C; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Gagliani N; Section of Molecular Immunology and Gastroenterology, Center of Internal Medicine, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Cordiglieri C; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520.
  • Mazzara S; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Ranzani V; Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institute and University Hospital, 17176 Stockholm, Sweden.
  • Rottoli E; Immunology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Curti S; Integrative Biology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Penatti A; Integrative Biology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Karnani B; Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
  • Kobayashi Y; Integrative Biology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Crosti M; Azienda Socio Sanitaria Territoriale Gaetano Pini, 20122 Milan, Italy.
  • Bombaci M; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • van Hamburg JP; Department of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520.
  • Rossetti G; Autoimmunity Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Gualtierotti R; Immunology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Gerosa M; Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center (UMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • Gatti S; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
  • Torretta S; Amsterdam Rheumatology and Immunology Center, Academic Medical Center, 1007 MB Amsterdam, The Netherlands.
  • Pignataro L; Integrative Biology Laboratory, National Institute of Molecular Genetics "Romeo ed Enrica Invernizzi," 20122 Milan, Italy.
  • Tas SW; Azienda Socio Sanitaria Territoriale Gaetano Pini, 20122 Milan, Italy.
  • Abrignani S; Azienda Socio Sanitaria Territoriale Gaetano Pini, 20122 Milan, Italy.
  • Pagani M; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Grassi F; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Meroni PL; Department of Clinical Science and Community Health (DISCCO), University of Milan, 20122 Milan, Italy.
  • Flavell RA; Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • Geginat J; Department of Clinical Science and Community Health (DISCCO), University of Milan, 20122 Milan, Italy.
Proc Natl Acad Sci U S A ; 117(13): 7305-7316, 2020 03 31.
Article em En | MEDLINE | ID: mdl-32184325
Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Interleucina-10 / Linfócitos T Auxiliares-Indutores / Receptores CCR6 / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Child / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Interleucina-10 / Linfócitos T Auxiliares-Indutores / Receptores CCR6 / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Adult / Animals / Child / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Itália